The Grapefruit Warning and CBD: What It Means for Your Medicines

Maybe someone told you to "treat CBD like grapefruit," and you wondered why. We don't give doses or recommend products.

At a glance

What the grapefruit warning means

The FDA has required some prescription and over-the-counter drugs taken by mouth to carry a warning against grapefruit juice or grapefruit (FDA 2021).

Enzymes are proteins that break medicines down. Many drugs are broken down by an enzyme called CYP3A4 in the small intestine. Grapefruit juice can block it, so more of the drug enters the blood and stays longer, which can mean more side effects (FDA 2021).

The active ingredients are natural chemicals called furanocoumarins. In a randomized study of 18 volunteers, grapefruit juice roughly doubled blood levels of the medicine felodipine compared with orange juice, but the same juice with its furanocoumarins removed did not; the effect happens in the gut, not the liver (Paine 2006). In 25 volunteers, one 300 mL glass raised levels of midazolam, a CYP3A test drug, by 65%; the effect faded with a half-life of about 23 hours and was largely gone within 3 days, consistent with the gut making new enzyme (Greenblatt 2003).

Strength of evidence: strong — many controlled studies and FDA-required label warnings.

Is there an official grapefruit warning for CBD?

We could not find one. The FDA's consumer page on CBD warns that CBD "can affect how other drugs you are taking work, potentially causing serious side effects," but does not mention grapefruit (FDA 2020). CBD products other than the prescription medicine Epidiolex have not been evaluated by the FDA for how they could interact with drugs or foods (FDA 2020).

Some FDA-approved labels do give specific CBD instructions. The label of Epidiolex, the FDA-approved prescription CBD, lists interactions enzyme by enzyme without using the word grapefruit (Epidiolex label 2026), and the tacrolimus and everolimus labels name CBD directly (Prograf label 2023; Afinitor label 2026).

Source type: an FDA consumer information page (not a regulation or formal guidance; content current as of March 5, 2020) and FDA-approved prescribing information (labeling).

Where CBD and grapefruit overlap, and where they don't

According to the Epidiolex label, CBD is broken down mainly in the liver, and also in the gut, by CYP2C19, CYP3A4 and UGT enzymes. CBD is a moderate inhibitor (slower-downer) of CYP2C19 and a weak inhibitor of CYP1A2, and it also affects CYP2C8, CYP2B6 and UGT1A9. It can affect P-gp, a pump in the gut wall that pushes some drugs back out; the label groups everolimus, whose levels CBD raised about 2.5-fold, with the drugs this pump handles. CBD may also lower the active form of some drugs, such as clopidogrel (Epidiolex label 2026).

For CYP3A4, the grapefruit enzyme, results are mixed:

• In healthy volunteers, prescription CBD (750 mg twice a day) did not change levels of midazolam (Epidiolex label 2026).
• In 18 healthy adults, one brownie with a CBD-dominant cannabis extract (640 mg CBD plus 20 mg THC) raised midazolam by 56% (Bansal 2023).
• With tacrolimus, CBD raised peak levels without changing how fast the drug left the body; the researchers think the effect most likely happens in the gut and "may be similar to that of grapefruit," though they list other possible explanations (So 2025).

Strength of evidence: moderate — small drug-level studies in healthy volunteers (some without placebo), with differing CYP3A4 results.

Interactions documented in people

A 2024 review of 31 reports involving cannabis, THC or CBD found interactions with warfarin, valproate, tacrolimus and sirolimus the most widely reported and possibly the riskiest (Nachnani 2024).

• Clobazam (epilepsy): Prescription CBD raised N-desmethylclobazam, the active substance clobazam turns into, about 3-fold; the label suggests considering a lower clobazam dose if side effects appear (Epidiolex label 2026). In 13 children it rose by an average of 500%; side effects in 10 eased when clobazam was lowered (Geffrey 2015). Strength of evidence: strong. CBD and clobazam
• Valproate: The issue is the liver, not the blood level. In Epidiolex trials for Lennox–Gastaut and Dravet syndromes, the liver enzyme ALT rose above 3 times normal in 21% of patients also on valproate (30% with valproate plus clobazam) versus 3% on neither; CBD did not change valproate levels in healthy volunteers (Epidiolex label 2026). Strength of evidence: strong. CBD and valproate
• Tacrolimus (transplant): In an interim analysis of 12 healthy volunteers on prescription CBD (up to 5 mg/kg twice a day), tacrolimus peak levels rose 4.2-fold and total exposure 3.1-fold (So 2025). One patient taking 2,000–2,900 mg of CBD a day had about a 3-fold rise (Leino 2019); in 7 kidney transplant patients taking 100–300 mg a day, levels varied (Cuñetti 2018). The tacrolimus label warns about CBD (Prograf label 2023). Strength of evidence: moderate — one small drug-level study plus case reports. CBD and tacrolimus
• Everolimus and sirolimus: Prescription CBD (12.5 mg/kg twice a day) raised everolimus about 2.5-fold in healthy adults (Wray 2023). In 25 patients with tuberous sclerosis complex, everolimus or sirolimus levels rose significantly in 76% after CBD was added (Ebrahimi-Fakhari 2020). The Epidiolex label recommends monitoring everolimus levels and says sirolimus levels may also rise (Epidiolex label 2026). Strength of evidence: strong for everolimus, limited for sirolimus. CBD with everolimus and sirolimus
• Warfarin (blood thinner): In a man who started prescription CBD, the INR clotting test rose as high as 6.86 and his warfarin dose was eventually cut by about 30% (Grayson 2018); a second patient needed about 20% less (Cortopassi 2020). A review of seven case reports of warfarin with cannabis products (THC or CBD) rated the evidence very low quality; doses were very high or unknown (Smythe 2023). Strength of evidence: low — case reports only. CBD and warfarin

Statins, blood pressure medicines and other "grapefruit drugs"

The FDA's examples of drugs grapefruit can affect include some statins (simvastatin, atorvastatin), some blood pressure drugs (nifedipine), some transplant drugs (cyclosporine), buspirone and amiodarone; not every drug in these groups is affected (FDA 2021).

A grapefruit warning does not prove a CBD interaction. In a November 2026 PubMed search, we found no published human study of CBD with statins or calcium channel blockers. A 2026 review says cannabinoids inhibit CYP3A4 and could potentially raise exposure to statins, calcium channel blockers and some heart drugs (Papakyriakopoulou 2026).

Blood pressure medicines raise a separate issue: CBD itself lowered 24-hour systolic pressure by about 4.8 mmHg versus placebo in 70 people with high blood pressure (Dujic 2024), and a review of four small trials found lower systolic pressure in all of them, with no serious heart events (Roberts 2026). In theory, this could add to a medicine's effect.

The tacrolimus label carries both warnings: it says to avoid grapefruit and, separately, to watch levels closely with CBD (Prograf label 2023).

Strength of evidence: very low for statins and calcium channel blockers (theory only); low to moderate for CBD's blood pressure effect (small, short trials). More: heart and blood pressure medicines, immunosuppressants, blood thinners.

Do the dose and the product matter?

Probably. Most studies used prescription CBD at 750 mg twice a day or 5–12.5 mg per kg twice a day (Epidiolex label 2026; So 2025; Wray 2023). The tacrolimus researchers note that their dose far exceeded the median over-the-counter amount (about 0.6 mg per kg a day) and that effects at lower amounts are unknown (So 2025). The everolimus label says the effect of CBD products other than the prescription solution is unknown (Afinitor label 2026).

A computer model built from the brownie study predicted that even 20 mg of CBD twice a day for a week could raise exposure to CYP2C19, CYP3A or CYP1A2 drugs by more than 25%; this was a prediction, not a measurement (Bansal 2023). An 85-year-old on warfarin using a product held in the mouth, with about 5 mg of CBD and a little THC a day, had no major INR swings over about 11 months (Thomas 2022).

Strength of evidence: low — very few studies at consumer-level amounts, and products differ.

When to talk to a doctor or pharmacist

• Before starting CBD, if a medicine you take carries a grapefruit warning, treats epilepsy or transplant rejection, thins the blood, or needs regular blood tests. The FDA advises asking your pharmacist whether grapefruit affects your drug (FDA 2021); ask about CBD at the same time.
• Bring the product or a photo of its label, showing the product type, the amount of CBD and whether it contains THC (reading labels).
• Don't stop or change a prescribed medicine on your own. The US Medication Guide for prescription CBD says not to start or stop other medicines without talking to your healthcare provider (Epidiolex label 2026). Stopping CBD matters too: the everolimus label tells doctors to go back to the earlier dose once prescription CBD has been stopped for 3 days (Afinitor label 2026).
• Ask whether monitoring makes sense, such as drug levels, INR or liver tests; labels call for drug-level checks with tacrolimus and everolimus (Prograf label 2023; Epidiolex label 2026).

Look up each medicine in our drug interaction checker.

Frequently asked questions

References